Impact of Vitamin D3 on Carbonyl-Oxidative Stress and Matrix Metalloproteinases after Acute Intracerebral Hemorrhage in Rats with Type 2 Diabetes Mellitus

Abstract

Introduction: Diabetes mellitus is associated with the development of carbonyl-oxidative stress (COS) and an increased risk of a cerebral hemorrhage. Vitamin D3 is considered an additional drug to have an impact on COS and proteolysis in the extracellular matrix. Objective: The study aimed to evaluate the impact of D3 on the COS-markers and matrix metallo-proteinases MMP2/MMP9 activity after acute intracerebral hemorrhage (ICH) in rats with experimental type 2 diabetes mellitus (Т2DM) compared to metformin (Met). Methods: T2DM was induced in rats via the intraperitoneal injection of streptozotocin (STZ) and nicotinamide (NA), ICH – by microinjection of bacterial collagenase into the striatum. Rats were randomized into five groups: 1 – intact animals (n = 8), 2 – T2DM (n = 9); 3 – T2DM+ICH (n = 7); 4 – T2DM+ICH+Met (n = 7); 5 – T2DM+ICH+D3 (n = 7). Blood glucose, glycated hemoglobin, and oral glucose tolerance test (OGTT) were assessed using commercial kits. Advanced oxidation protein products (AOPP), protein carbonyls (PC370/430), and ischemia-modified albumin (IMA) were measured by spectrophotometry, advanced glycation end products (AGEs) by quantitative fluorescence, and matrix metalloproteinases MMP2/9 by gelatin zymography. Results: D3 does not significantly affect the glucose level and OGTT in rats with T2DM+ICH. How-ever, it reduces AOPP, PC, and AGEs, thus reducing the COS index. In contrast, the activity of proMMP9 increases after D3 administration. These effects of D3 have been reported to be stronger and sometimes opposite to those of metformin. Conclusion: D3 supplementation may decrease the negative consequences of a cerebral hemorrhage in T2DM by reducing COS and preventing the accumulation of COS-modified proteins in the brain by regulating the expression and activity of MMP9.